tbuckley/cabot-search huggingface dataset:
Abstract 11637: Myocardial Metabolic Dysregulation and Right Ventricular Outcomes After Surgery for Advanced Heart Failure
Authors: Kamrouz Ghadimi, Stephanie Giamberardino, Maggie Nguyen, Jhana Parikh, Jacob Schroder, Erick Lorenzana-Saldivar, Will Thompson, Sudarshan Rajagopal, Benjamin Bryner, Carmelo A Milano, Svati H Shah
Journal: Circulation (2022)

Introduction: Inhaled pulmonary vasodilators (iPVD) help prevent right heart failure (RHF) by lowering PVR after surgery. However, variable change in PVR is seen in response to iPVD. As metabolism is central to cardiomyocyte function, we evaluated the role of right ventricular (RV) myocardial metabolism in iPVD response heterogeneity. Hypothesis: We previously identified plasma metabolic biomarkers as potential reporters of response heterogeneity and posited here that these key metabolites change in parallel with changes in RV phenotypes. Methods: We evaluated 63 LVAD or heart transplant recipients with precapillary pulmonary hypertension before surgery from a recent randomized trial (INSPIRE-FLO, NCT03081052). All participants received iPVD after heart-lung bypass through postoperative day 1 (pod 1). Targeted profiling of &gt; 500 metabolites (MxP® Quant 500, Biocrates) was performed in baseline and pod 1 plasma, and in RV free-wall full-thickness biopsies from LVAD recipients. Principal components analysis (PCA) was used for metabolite dimensionality reduction. Generalized linear models were used to assess the association of percent change (%Δ) in metabolite factors with (1) %Δ PVR (baseline to pod1); (2) responder, PVR &lt; 3 Wood U vs. non-responder, PVR ≥ 3 Wood U, on pod 1); (3) RHF after surgery. Results: PCA identified 21 factors with 204 metabolites clustering in biologically consistent pathways. Of these, %Δ in factor 8 (glycine and eight glycerophospholipids, GPs) were positively correlated with %Δ PVR (P &lt; 0.05). There was a trend for association in %Δ in factors 1 and 12 (ceramides, other GPs, amino acids: glutamate, aspartate, alanine, glutamine) and %Δ PVR (both P &lt; 0.10, negatively correlated). There was a trend for association in %Δ in factor 7 (long chain acylcarnitines) and subsequent RHF (P = 0.08, positively correlated). No metabolites were associated with responder status. Plasma levels of select metabolites in factors 1 and 12 were positively correlated with RV myocardial levels (P &lt; 0.05), suggesting a myocardial source. Conclusions: Leveraging a unique clinical trial cohort, we identified substrates of amino acid and fatty acid mitochondrial ß-oxidation metabolism in RV myocardium that may serve as biomarkers of metabolism in RHF.
Abstract 12212: Heart Failure With Preserved Ejection Fraction: A Cardiologist Disorder or a Nephrologist Problem? Analysis From a Largely Hispanic Population
Authors: Rahul N Patel, Akash Sharma, Roma Ahuja, Nghia Tran, Aliseiya Garza, Shweta Bansal
Journal: Circulation (2022)

Introduction: Heart failure with preserved ejection fraction (HFpEF) has been recognized as a multisystem process and chronic kidney disease (CKD) plays a central role in this paradigm. However, racial/ethnic variability and prevalence of CKD are not well described. Hypothesis: We hypothesize that the South Texas Hispanic patient population has a different phenotypic expression of HFpEF compared to the largely White population in the EMPEROR-Preserved trial. Methods: Consecutive HFpEF patients (total n=204) were identified from a HF population screened for a clinical trial from 2019-2020 (n=188) and inpatients with HF exacerbation during 2021 (n=16) at University Hospital. HFpEF was defined as symptomatic HF with left ventricular ejection fraction (LVEF) &gt;40% on Echo. Clinical and lab variables were collected ±1 year from Echo date. Race/ethnicity was self-reported. CKD was identified from the problem list. Rates were compared with EMEPROR-Preserved trial’s HFpEF population which was largely White. Results: Of 204 HFpEF patients, 9 were Black, 14 were from other races, and due to small size were excluded from the analysis. Majority of the study population were Hispanics (130 of 181, 72%). LVEF was 40-50% in 31% of the study population. Table 1 demonstrates characteristics by EMPEROR population, and Hispanics and non-Hispanic Whites (NHW) in our analysis. Of significance, our population was younger, had DM2, CAD, CKD, and obesity at higher rates, and AFib and BNP at lower rates as compared to EMPEROR population. The differences in Hispanics and NHW were unremarkable except more HTN and lower eGFR in Hispanics. Conclusions: Hispanic patients with HFpEF have more frequent diabetes, CKD and CAD as compared to White population in EMPEROR-Preserved trial. In context of this observation and recent success of newer agents as empagliflozin, a multispecialty integrative approach is strongly warranted for management of HFpEF patient population.
Abstract 11767: Alarmingly Rising Trends in Cardiovascular Disease Risk Factors and Atrial Fibrillation in Young [18-44 Years] Asian Patients: A Nationwide Analysis Between 2016 and 2019
Authors: Nanush Damarlapally, Nishtha Rana, Dr. Vaishnavi Arote, Mounika Reddy Vadiyala, Pranjali Singh, Birgurman Singh, Gokul Paidi, Rineetha Tandra, Hardik Patel, Avilash Mondal, Rupak Desai
Journal: Circulation (2022)

Background: Traditional cardiovascular disease (CVD) risk factors can increase the risk of Atrial Fibrillation (AF) even in young adults. With rising trends in CVD in the Asian population, we aimed to assess the prevalence and disparities of major modifiable risk factors for CVD and AF in the young Asians hospitalized in the US. Methods: The National Inpatient Sample (2016-2019) was used to estimate the temporal trends in modifiable CVD risk factors among young (18-44 years) Asian hospitalizations and evaluated disparities by sex. Also, we assessed the prevalence of AF in young Asians hospitalized with vs. without atleast one CVD risk factor. Results: From 2016 through 2019, a total of 1,324,259 young Asian admissions (Male 85%, age 18-44 years) were analyzed, the highest increase was noted for Obesity (1.8%) followed by Diabetes (1.3%). Males demonstrated the most prominent prevalence of Obesity (2.1%) and Hypertension (1.7%) as compared to the female population (1.7% and 0.4%), respectively. The incidence of AF in patients with at least one CVD risk factor increased by 0.4% (males 0.9% vs females 0.15%), (OR 2.80, 95%CI 2.44-3.21, p&lt;0.001). Conclusion: The prevalence of modifiable risk factors for CVD are increasing at a steady pace in the young Asian population. There is a need for urgent preventive and curative strategies to decrease the overall burden of CVD in this population.
Abstract 12706: Stroke Risk and Oral Anticoagulation Use With Extended Cardiac Monitoring for Atrial Fibrillation versus Usual Care: A Systematic Review With Meta-Analysis
Authors: Chris Cheung, Blair MacDonald, Ricky Turgeon, Thalia FIELD, Michael D Hill, Luciano Sposato, Andrew Ha, Atul Verma, Subodh Verma, Jesper Hastrup Svendsen, Jacob M Larsen, Søren Diederichsen, Koh Keng Tat, Jason G Andrade
Journal: Circulation (2022)

INTRODUCTION: Prolonged cardiac monitoring is frequently used to detect atrial fibrillation (AF) in high-risk populations, with the goal of preventing thromboembolic events. We sought to determine the impact of prolonged cardiac monitoring on the incidence of stroke and systemic embolism (SSE) or transient ischemic attack (TIA) METHODS: We performed a systematic review and meta-analysis of randomized trials evaluating prolonged monitoring versus usual care (PROSPERO #CRD42021277611). Studies were identified through CENTRAL, MEDLINE, and Embase. We included studies with ≥100 participants and ≥30 days follow-up. The primary outcome was a composite of SSE/TIA, as reported in the original trials. Secondary outcomes included AF detection, oral anticoagulation (OAC) initiation, and major bleeding. Sensitivity analysis examining the impact of monitoring device, and indication for monitoring were performed. Meta-analyses were performed with R using a random-effects model. RESULTS: From 1411 records, we included 9 RCTs (n = 10,205). Mean age was 70 years, 40% were female, and mean CHADS2 score was 4.0. Studies used implantable cardiac monitors (n = 4), external cardiac monitors (n = 3), or handheld ECG devices (n = 2). Study populations included post-stroke (n = 5), high risk for AF or stroke (n = 2), and post-cardiac surgery (n = 1). Mean follow-up was 16 months (range 3-65). Extended monitoring did not significantly reduce the primary outcome (Figure, random effects risk ratio [RR] 0.87, 95% confidence interval [CI] 0.72-1.06, I2 = 0%) or its individual components. Extended monitoring increased AF detection (RR 4.56, 95% CI 3.01-6.92, I2 = 65%) and OAC usage (RR 2.25, 95% CI 2.01-2.53, I2 = 0%), but did not impact major bleeding (RR 1.23, 95% CI 0.84-1.82, I2 = 0%). CONCLUSION: Prolonged monitoring was associated with increased AF detection and OAC use, without significantly reducing the occurrence of thromboembolic events.
Abstract 12349: Can Biomarkers and Risk Scores Be Used to Select Patients With Type 2 Diabetes Mellitus for Testing for Subclinical Left Ventricular Dysfunction
Authors: Amera Halabi, Elizabeth Potter, Hong Hilda Yang, Leah Wright, Julian W Sacre, Jonathan Shaw, Thomas Marwick
Journal: Circulation (2022)

Background: Subclinical LV dysfunction (LVD) identifies heart failure (HF) risk in type 2 diabetes mellitus (T2DM). Hypothesis: Clinical scores (ARIC HF and WATCH-DM) and NTpBNP can be used as screening tests to identify which people should undergo echo. Methods: 803 asymptomatic subjects (69 years [IQR 65-73], 36% female) with T2DM were prospectively recruited from three community-based populations. All underwent a comprehensive echo to identify abnormal global longitudinal strain (GLS &gt; -16%), diastolic function (E/e’ &gt; 14 or e’&lt;8cm/s), left atrial volume index (LAV&gt;34ml/m 2 ) or LV hypertrophy (LV mass index&gt;88g/m 2 (F)&gt;102g/m 2 (M)). ARIC HF risk at 4 years and WATCH-DM scores were calculated from clinical data. NTpBNP was measured using an electro-chemiluminescence assay. Results: In the cohort, 126 (17%) had an abnormal GLS, 16 (2%) elevated E/e’, 266 (33%) had impaired e’, 351 (44%) had increased LAV and 113 (14%) had LV hypertrophy. Median NTpBNP level was 50pg/mL [25-101]. Clinical scores corresponded to expected HF risk (ARIC-HF 8% [4-12]; WATCH-DM 10 points [8-12]). NTpBNP was weakly associated with GLS after adjustments for age, body-mass index, and renal function (β=0.004 [95% CI 0.003 to 0.004], p&lt;0.001). Similar trends were observed with ARIC HF (β=0.07 [0.05 to 0.09], p&lt;0.001) and WATCH-DM (β=0.19 [0.13 to 0.25], p&lt;0.001) in univariable analyses. None of the risk assessment tools provided a satisfactory AUC for detection of abnormal GLS, diastolic indices or LV mass (Table) ( p =0.804). Development of cut-points to optimize sensitivity (to 90%) led to an unacceptably low specificity (Table). Conclusion: Although risk assessment based on clinical scores or biomarkers would be desirable to stratify HF risk in people with T2DM, they show a weak relationship with subclinical LV dysfunction.
Abstract 11967: Microrna-150 Overexpression Blunts Maladaptive Cardiac Remodeling in Mice With Cardiomyocyte-Specific Loss of β-Arrestin-Mediated β <sub>1</sub> -Adrenergic Receptor Signaling
Authors: Bruno Moukette, Satoshi Kawaguchi, Marisa Sepulveda, Il-man Kim
Journal: Circulation (2022)

Background and Aims: β-arrestins transduce alternative pathways independent of G protein signaling, a concept known as β-arrestin-biased signaling that is promoted by G protein-coupled receptor kinase (GRK) 5/6 phosphorylation on β-adrenergic receptors (βARs). The β 1 AR is found primarily in the heart (mainly in cardiomyocytes [CMs]) and β-arrestin-mediated β 1 AR signaling elicits cardioprotection by CM survival. We showed that a small noncoding RNA (ncRNA), microRNA-150 (miR-150) is upregulated by the β-blocker carvedilol acting through β-arrestin-mediated β 1 AR signaling, and that CM miR-150 confers cardioprotection (see Figure). Here, we investigate if miR-150 in part rescues maladaptive cardiac remodeling seen in mice with CM-specific abrogation of β-arrestin-mediated β 1 AR signaling. Methods and Results: Using CM-specific transgenic (TG) mice expressing a mutant β 1 AR (i.e. GRK - β 1 AR exhibiting impairment in β-arrestin-mediated β 1 AR signaling and miR-150 activation by carvedilol), we first develop a novel double TG (DTG) mouse line overexpressing miR-150 and CM-specific GRK - β 1 AR. We demonstrate that miR-150 improves maladaptive cardiac remodeling observed in CM-specific GRK - β 1 AR TG mice after chronic catecholamine stimulation. Genome-wide circular RNA, long ncRNA (lncRNA) and mRNA profiling analyses in DTG mouse hearts unveil a subset of cardiac ncRNAs and genes as heretofore unrecognized mechanisms for miR-150’s beneficial effects. We further show that lncRNA Gm41664 and Gdap1l1 have miR-150 binding sites, and that they are direct novel upstream and downstream regulators of miR-150. Lastly, protective roles of miR-150 in CMs are in part attributed to the functional repression of pro-apoptotic Gdap1l1 and are mitigated by pro-apoptotic Gm41664 (see Figure). Conclusions: Our findings support that miR-150 contributes significantly to β 1 AR/β-arrestin-mediated cardioprotection by regulating a unique ncRNA and gene signature in CMs.
Abstract 11511: Stem Cell-Derived Exosome Nebulization Therapy (SCENT) Promotes Cardiac Repair After Myocardial Infarction by Inhibiting CD36
Authors: Junlang Li, Shenghuan Sun, DASHUAI ZHU, Atul Butte, Ke Cheng
Journal: Circulation (2022)

Introduction: Stem cell-derived exosomes are promising therapeutics for cardiac repair after injury. Since they have short half-life in vivo, efficient exosome therapies need repeated dosing. Here, we develop a noninvasive and repeatable method for exosome delivery via a nebulizer after myocardial infarction (MI), named Stem Cell-Derived Exosome Nebulization Therapy (SCENT). Methods: Lung spheroid cell-derived-exosomes were isolated from secretome by ultrafiltration and characterized by a Zetasizer. We labelled them with a NIR-680 dye, before delivering them to C57BL/6 mice with MI model via a nebulizer for 7 consecutive days. IVIS live imaging and fluorescent microscopy was used to detect the biodistribution of exosomes in vivo and ex vivo. Echocardiographies were performed to monitor the cardiac function after SCENT in MI mouse and histological analysis helped investigating the myocardial repair, in comparison with the controls. Single-cell sequencing of the whole heart was performed to explore the mechanism of action after SCENT. Results: Homing of exosomes to the ischemic heart after SCENT was detected by immunofluorescence microscopy (Fig. 1a). SCENT led to significantly improved left ventricular function to our mouse MI model at 2 weeks (EF: 66.97 ± 2.49%), compared to that of MI control (EF: 36.13 ± 3.57%) (Fig. 1b) , along with reduced infarct size (Fig. 1c). Single-cell sequencing revealed a significant downregulation of CD36 in cardiac endothelial cells, which suppressed the transport and uptake of fatty acids in myocardium, leading to a compensatory increase in glucose utilization and cardiomyocyte proliferation (Fig. 1d,e) . Conclusions: Exosomes delivered by SCENT were recruited to the ischemic heart, which promoted function recovery and cardiac repair in a mouse MI model. This therapeutic effect was attributed to the inhibition of endothelial CD36. SCENT gives a promising solution for the repeatable and noninvasive treatment for heart repair.
Abstract 12149: Assessment of Cryoballoon Occlusion Shift From the Pulmonary Vein Ostium Following Freeze Initiation Using a Dielectric Imaging System
Authors: Emrie D Tomaiko-Clark, J Peter Weiss, Michael Zawaneh, Wilber Su
Journal: Circulation (2022)

Introduction: Cryoballoon ablation for atrial fibrillation (AF) has been widely adopted clinically. However, dislodgement from the pulmonary vein (PV) ostium following freeze initiation commonly occurs due to a sudden rise in balloon pressure, known as the “pop-out” phenomenon. This can often only be partially detected using continuous color Doppler or repeat angiography after the initiation of freeze. We aim to access the incidence of this phenomenon using the dielectric imaging system in comparison to intracardiac echocardiography (ICE). Methods: Ten patients underwent de novo cryoballoon ablation for paroxysmal or persistent AF with the use of the KODEX-EPD dielectric imaging system (Philips, Amsterdam, Netherlands). A baseline assessment and injection were performed pre-ablation followed by analysis of occulsion via the KODEX Occlusion Viewer. Simultaneous assessment was performed by the operator utilizing ICE. Repeat assessment with injection was performed after ablation start to assess whether the cryoballoon remained occluded on ICE and by KODEX’s occlusion assessment. Results: There was a high correlation between KODEX and ICE for assessment of balloon occlusion prior to ablation (91.7±23.6%). KODEX demonstrated an overall sensitivity (88.6%), specificity (75.0%), positive predictive value (76.5%), and negative predictive value (87.8%) of the occlusion tool validated by ICE. Both imaging modalities detected a leak after initial full occlusion, an incidence of 24.3% on Kodex and 23.8% on ICE. Conclusions: Balloon contact with the PV is vital for an effective, transmural lesion. The dielectric imaging system and ICE confirmed high incidence of this “pop-out” phenomenon, which can lead to incomplete PV isolation. The KODEX-EPD occlusion tool is highly sensitive and specific to assist in the identification of this phenomenon and may improve the outcome for cryoballoon procedures. In the future a more compliant cryoballoon design, without a shift in balloon pressure during ablation, may avoid this phenomenon.
Abstract 12307: Exercise-Induced Ventricular Fibrillation in Patients with Brugada Syndrome Phenotype
Authors: Akira Ueoka, Hiroshi Morita, Tomofumi Mizuno, Takuro Masuda, Saori Asada, Masakazu Miyamoto, satoshi kawada, koji nakagawa, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito
Journal: Circulation (2022)

Introduction: Ventricular fibrillation (VF) in Brugada syndrome (BS) patients are thought to be triggered by vagal nerve activation, which leads to sudden cardiac arrest (SCA) at rest or while asleep. Generally, exercise is not considered as trigger of SCA in BS patients. Aim: To report 2 rare cases of patients with BS phenotype developing exercise-induced ventricular (VF). Case reports: Case 1: 48 year-old male developed SCA during marathon running and was successfully resuscitated with cardiopulmonary resuscitation (CPR). The stored automatic external defibrillator (AED) electrogram (ECG) showed VF. The 12-lead ECG did not show abnormal morphology, however sodium channel blocker challenge test (intravenous injection of pilsicainide, a pure sodium channel blocker 1mg/Kg) unmasked typical type-1 BS ECG. The treadmill stress test induced single premature ventricular contraction by Bruce protocol, and ventricular tachycardia by a flat-out dash without a run-up. Genetic analysis did not show mutation of SCN5A gene. Case 2: 18 year-old male experienced SCA while playing basketball and was successfully resuscitated with CPR. The stored ECG record of AED showed VF. The 12-lead ECG showed normal result, then we performed the drug challenge test. Pilsicainide unmasked typical type-1 BS ECG. He also had exercise-induced atrial fibrillation (AF) and experienced inappropriate shock delivery from implantable cardioverter defibrillator. The treadmill stress test by Bruce protocol did not induce any ventricular arrhythmias. We avoided a flat-out dash protocol because of possibility of exercise-induced AF. Genetic analysis did not show SCN5A mutation. Conclusion: These 2 rare cases of drug-induced BS phenotype developing exercise-induced VF highlight important role of exercise testing as risk stratification tool in certain BS patients.
Abstract 12383: Large Field-of-View Intravascular Ultrasound for Peri-Procedural Assessment of Stent Frame Expansion After Transcatheter Heart Valve-in-Valve
Authors: LUKASZ KALINCZUK, Wiktor Skotarczak, Zbigniew Chmielak, Maciej Dabrowski, Rafal Wolny, Patrycjusz Stoklosa, Olgierd Wozniak, Piotr Hoffman, Ilona Michalowska, Marcin Demkow, Gary S Mintz, Lars Sondergaard, Adam R Witkowski
Journal: Circulation (2022)

Introduction. It is unknown whether large field-of-view intravascular ultrasound (IVUS) can be a valid peri-procedural imaging tool to assess actual expansion of transcatheter heart valve (THV) during valve-in-valve procedures. Hypothesis. To compare % expansion of SAPIEN 3 THV measured with peri-procedural IVUS versus post-procedural cardiac gated contrast multi-slice computer tomography (MSCT). Expansion was defined as actual outer frame area/nominal area x 100%. Methods. Studied were patients with successful valve-in-valve for failed surgical mitral and tricuspid bioprosthetic valves. All underwent peri-procedural IVUS using 10MHz Vision PV035 (Philips North America Corporation, Andover, USA) and post-procedural MSCT (SOMATOM Definition Flash, Dual Source, SIEMENS). IVUS and MSCT (Syngo Via, Siemens, Germany) measurements were off -line and done at 1-mm step along the entire height of SAPIEN 3 THV (height 18, 20 and 22 mm for the Sapien THV 23, 26 and 29 mm, respectively). Results. Five patients (68.8±11.2 years, 3 female) were treated for failed surgical mitral (n=3) and tricuspid (2) bioprosthetic valves using SAPIEN 3 THV size 23mm (n=1), 26mm (n=1), and 29mm (n=3). Mean peri-procedural and pre-discharge residual transvalvular gradient differed substantially (1.9±0.9 vs 7.9±1.1mmHg, p=0.001). In total, 104 corresponding cross-sections of the THVs were measured with both IVUS and MSCT. Actual outer-frame SAPIEN 3 expansion was smaller within the lengths of inflow and mid segment (overlapping the ring) than in the outflow, being substantially smaller than nominal (Fig 1). Overall, there was very good agreement between % expansion of THV stent frame assessed in IVUS and MSCT (93.5%±13.3% vs 96.3%±11.3%; r =0.976 and p&lt;0.001). Conclusions. Peri-procedural use of large field-of-view IVUS offers an accurate insight into actual THV expansion deployed valve-in-valve. Figure 1. % expansion of SAPIEN 3 measured in IVUS and MSCT.